These studies are directed to the use of immunological and immunochemical techniques to define factors which modulate synthesis and secretion of certain gastrointestinal peptides, with particular emphasis on gastrin, in experimental animals, in normal man, and in certain diseases of the gastrointestinal tract characterized by alterations in hormone synthesis and secretion. Studies will be conducted in which the synthesis and secretion of gastrin by antral mucosal explants using the organ culture technique will be determined. Synthesis of gastrin will be assessed by the progressive incorporation of (3H)-amino acids into gastrin purified by immunoprecipation techniques, with gastrin release measured by radioimmunoassay. Effects of factors which modify synthesis and secretion will be evaluated, including examination of the adenylate cyclase-cyclic AMP system, effects of calcium on gastrin synthesis and secretion, and effects of various gastrointestinal hormones on synthesis and secretion of gastrin. The role of the microtubular-microfilamentous system in gastrin synthesis and secretion will also be evaluated by examination of the effects of agents which modify this system. Studies will be performed to determine the molecular species of gastrin synthesized and released by antral and duodenal mucosa and by Zollinger-Ellison gastrinoma, including studies to define potential precursor-product relationships between big gastrin (G-34) and heptadecapeptide gastrin (G-17). Techniques to be used include definition of molecular species of gastrin by use of antibodies with precisely defined regional specificity for portions of the gastrin molecule. Using the antral organ explant system, synthesis and secretion of other peptides of origin in the gastrointestinal tract, including secretin, somatostatin, vasoactive intestinal peptide, and gastric inhibitory peptide, will also be examined.